In the United States, more than 70 million people are afflicted with chronic pain, which leads to billions of dollars spent for medical treatments and lost productivity yearly. Initial studies in our laboratory have described a compromised blood-brain barrier (BBB) associated with acute inflammatory pain. Physiologically, the BBB is the endothelial vasculature which permeates the brain. The BBB is critical to maintaining the regulated environment of the brain. The protein cytoarchitecture of the tight junctions (TJs) of the BBB are responsible for controlling paracellular permeability at the BBB. It has been well-established that the BBB is compromised in various disease states associated with TJ disregulation. The hypothesis of this proposal is that chronic inflammatory pain leads to a change in functional BBB integrity, which correlates with alterations in the transmembrane TJ proteins occludin, claudin-3 and claudin-5. These studies will provide new information related to the effect of chronic inflammatory pain on BBB integrity and the mechanisms underlying functional alterations in specific TJ proteins. Ultimately this grant may identify novel avenues for therapeutic intervention of inflammatory mediated disease states.